259 English Summary Figure 1. Graphical summary of Part 1: Immune response in animal burn models. PART 2: IMMUNE RESPONSE IN BURN PATIENTS Blood and burn tissue samples were collected to investigate the immune response in burn patients. Using both unsupervised and supervised flow cytometry as well as multiplex microscopy and immunoassays, the levels of immune cell subsets and inflammatory mediators present in the circulation (Chapter 4) and wound tissue (Chapter 5) were delineated. Longitudinal analyses using blood samples from 20 severely burned patients revealed an immediate surge of innate immune cells with initially a large contribution of immature neutrophils, but no increase in lymphocyte numbers. From the second week onward, shifts in T cell subpopulations were observed: there was an increase of CCR4 and CCR6 expressing cells and although regulatory T cell (Treg) numbers increased as well, the overall phenotype of the CD4+ T cells and Tregs appeared to be rather proinflammatory than anti-inflammatory. Simultaneously with leukocytosis, increased levels of various pro-inflammatory cytokines were found. 9
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